Women and men are at different risks for the onset, expression, and treatment response in a number of disorders that occur at different stages of development and throughout aging. The mechanisms that explain these sex differences or disorders specific to women are still unclear. The mission of our Harvard BIRCWH is to develop the next generation of scientist- clinicians as leaders in the field of women's health who will contribute to understanding sex-specific vulnerabilities to clinical disorders and those disorders specific to women. This competing renewal application seeks to continue to support an integrated interdisciplinary training program that is based on a translational approach to understanding differential incidences of specific disorders important for women's health. The program is modeled in the context of a lifespan perspective to identify etiologic mechanisms during fetal development, puberty, adulthood, and aging, with some focus on female-specific periods such as child- bearing years and menopause. Further, an underlying assumption of our BIRCWH program is that an understanding of the role of hormones and genes will provide the basis for understanding sex-specific vulnerabilities to clinical disorders. The Connors Center for Women's Health & Gender Biology at Brigham & Women's Hospital (BWH) is and will continue to be the home site for this endeavor, in the broader context of a Harvard-wide training program. The program capitalizes on the long tradition of interdisciplinary research in women's health with Mentors who already collaborate across institutions at BWH, Massachusetts General Hospital, Beth Israel-Deaconess Medical Center, Dana Farber Cancer Institute, McLean Hospital, Harvard School of Public Health, Harvard Medical School and the Eli & Edythe Broad Institute, Each of four Scholars is assigned a team of Mentors in order to operationalize the concept of training Scholars to think in a translational manner. Primary Mentors are in clinical or basic research and provide the site at which the Scholar works. Secondary Mentors are in basic or clinical research (as a counterpart to the Primary) and help to guide thinking, suggest coursework, and readings, depending on the Scholar's interest. Career Mentors advise Scholars in the relevant departmental and academic structures for career advancement. Mentors in Health Disparities expose Scholars to thinking about how the roles of hormones and genes in predicting morbidity are influenced by socioenvironmental factors. The Harvard BIRCWH program focuses on the following disorders, given either the known higher incidence in women than men and/or differential expression in women or the strengths of the Harvard community in women's health: Cardiovascular Disorders; Reproductive Endocrine & Neuroendocrine Disorders; Neuropsychiatric Disorders; Autoimmune Disorders; and Female Cancers (e.g. breast, ovarian & uterine). By capitalizing on the vast resources and faculty at Harvard, we would argue that Harvard is an ideal site for continuing to offer an integrated, interdisciplinary and truly translational program that is training the next generation of leaders in women's health. PUBLIC HEALTH RELEVANCE: Although there are significant sex differences in the expression and onset of major medical and psychiatric disorders, clinical decisions based on research are primarily based on data from men and may often be inappropriate for women. Thus, there is a strong need for the education and development of junior investigators who would commit their careers to studying the impact of sex and gender on clinical disorders. Their research programs will provide the basis for the development of sex-specific treatment approaches and public awareness as to the importance of these sex-specific health issues for families and society.